Abstract
Large-conductance calcium-activated potassium channels (maxi-K channels) have an essential role in the control of excitability and secretion. Only one gene Slo is known to encode maxi-K channels, which are sensitive to both membrane potential and intracellular calcium. We have isolated a potassium channel gene called Slack that is abundantly expressed in the nervous system. Slack channels rectify outwardly with a unitary conductance of about 25–65 pS and are inhibited by intracellular calcium. However, when Slack is co-expressed with Slo, channels with pharmacological properties and single-channel conductances that do not match either Slack or Slo are formed. The Slack/Slo channels have intermediate conductances of about 60–180 pS and are activated by cytoplasmic calcium. Our findings indicate that some intermediate-conductance channels in the nervous system may result from an interaction between Slack and Slo channel subunits.
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References
Nelson, M. T. et al. Relaxation of arterial smooth muscle by calcium sparks. Science 270, 633–637 (1995).
Trautmann, A. & Marty, A. Activation of Ca-dependent K channels by carbamoylcholine in rat lacrimal glands. Proc. Natl Acad. Sci. USA 81, 611–615 (1984).
Lingle, C. J., Solaro, C. R., Prakriya, M. & Ding, J. P. Calcium-activated potassium channels in adrenal chromaffin cells. Ion Channels 4, 261–301 (1996).
Wang, W., Hebert, S. C. & Giebisch, G. Renal K+ channels: structure and function. Annu. Rev. Physiol. 59, 413– 36 (1997).
Pacha, J., Frindt, G., Sackin, H. & Palmer, L. G. Apical maxi K channels in intercalated cells of CCT. Am. J. Physiol. 261, F696–F705 (1991).
Storm, J. F. Potassium currents in hippocampal pyramidal cells. Prog. Brain Res. 83, 161–187 (1990).
Lancaster, B., Nicoll, R. A. & Perkel, D. J. Calcium activates two types of potassium channels in rat hippocampal neurons in culture. J. Neurosci. 11, 23–30 (1991).
Petersen, O. H. & Maruyama, Y. Calcium-activated potassium channels and their role in secretion. Nature 307, 693–696 (1984).
Latorre, R., Oberhauser, A., Labarca, P. & Alvarez, O. Varieties of calcium-activated potassium channels Annu. Rev. Physiol. 51, 385–399 (1989).
Robitaille, R., Garcia, M. L., Kaczorowski, G. J. & Charlton, M. P. Functional colocalization of calcium and calcium-gated potassium channels in control of transmitter release. Neuron 11, 645–655 (1993).
Reinhart, P. H., Chung, S., Martin, B. L., Brautigan, D. L. & Levitan, I. B. Modulation of calcium-activated potassium channels from rat brain by protein kinase A and phosphatase 2A. J. Neurosci. 11, 1627–1635 (1991).
Chung, S. K., Reinhart, P. H., Martin, B. L., Brautigan, D. & Levitan, I. B. Protein kinase activity closely associated with a reconstituted calcium-activated potassium channel. Science 253, 560–562 (1991).
Sansom, S. C., Stockand, J. D., Hall, D. & Williams, B. Regulation of large calcium-activated potassium channels by protein phosphatase 2A. J. Biol. Chem. 272, 9902– 9906 (1997).
Dworetzky, S. I. et al. Phenotypic alteration of a human BK (hSlo) channel by hSlobeta subunit coexpression: Changes in blocker sensitivity, activation/relaxation and inactivation kinetics, and protein kinase A modulation. J. Neurosci. 16, 4543–4550 (1996).
McManus, O. B., et al. Functional role of the beta subunit of high conductance calcium-activated potassium channels. Neuron 14, 645– 650 (1995).
Wallner, M. et al. Characterization of and modulation by a beta-subunit of a human maxi KCa channel cloned from myometrium. Receptors Channels 3, 185–199 (1995).
Schopperle, W. M. et al. Slob, a novel protein that interacts with the Slowpoke calcium-dependent potassium channel. Neuron 20, 565– 573 (1998).
Xia, X. M., Hirschberg, B., Smolik, S., Forte, M. & Adelman, J. P. dSLo interacting protein 1, a novel protein that interacts with large-conductance calcium-activated potassium channels. J. Neurosci. 18, 2360– 2369 (1998).
Atkinson, N. S., Robertson, G. A. & Ganetzky, B. A component of calcium-activated potassium channels encoded by the Drosophila slo locus. Science 253, 551–555 (1991).
Adelman, J. P. et al. Calcium-activated potassium channels expressed from cloned complementary DNAs. Neuron 9, 206– 216 (1992).
Tseng-Crank, J. et al. Cloning, expression and distribution of functionally distinct Ca2+-activated K+ channel isoforms from human brain. Neuron 13, 1315– 1330 (1994).
Dworetzky, S. I., Trojnacki, J. T. & Gribkoff, V. K. Cloning and expression of a human large-conductance calcium-activated potassium channel. Mol. Brain Res. 27, 189–193 (1994).
Butler, A., Tsunoda, S., McCobb, D. P., Wei, A. & Salkoff, L. mSlo, a complex gene encoding "maxi" calcium-activated potassium channels. Science 261, 221–224 (1993).
McCobb, D. P. et al. A human calcium-activated potassium channel gene expressed in vascular smooth muscle. Am. J. Physiol. 267, H767–H777 (1995).
Saito, M., Nelson, C., Salkoff, L. & Lingle, C. J. A cysteine-rich domain defined by a novel exon in a slo variant in rat adrenal chromaffin cells and PC12 cells. J. Biol. Chem. 272, 11710–11717 (1997).
Navaratnam, D. S., Bell, T. J., Tu, T. D., Cohen, E. L. & Oberholtzer, J. C. Differential distribution of Ca2+-activated K+ channel splice variants among hair cells along the tonotopic axis of the chick cochlea. Neuron 19, 1077 –1085 (1997).
Rosenblatt, K. P., Sun, Z. P., Heller, S. & Hudspeth, A. J. Distribution of Ca2+-activated K+ channel isoforms along the tonotopic gradient of the chicken's cochlea. Neuron 19, 1061–1075 (1997).
Jones, E. M., Laus, C. & Fettiplace, R. Identification of Ca2+-activated K+ channel splice variants and their distribution in the turtle cochlea. Proc. R. Soc. Lond. 265, F>685–692 (1998).
Morita, T., Hanaoka, K., Morales, M. M., Montrose-Rafizadeh, C. & Guggino, W. B. Cloning and characterization of maxi K+ channel alpha-subunit in rabbit kidney. Am. J. Physiol. 273, F615– F624 (1997).
Dryer, S. E., Duorado, M. M. & Wisgirda, M. E. Characteristics of multiple Ca2+-activated K+ chanels in acutely dissocated ciliary ganglion neurons. J. Physiol. 443, 601–627 (1991).
Toro, L., Vaca, L. & Stefani, E. Calcium-activated potassium channels from coronary smooth muscle reconstituted in lipid bilayers. Am. J. Physiol. 260, H1779–H1789 (1991).
Sakaba, T., Ishikane, H. & Tachibana, M. Ca2+-activated K+ current at presynaptic terminals of goldfish retinal bipolar cells. Neurosci. Res. 27, 219–228 (1997).
Farley, J. & Rudy, B. Multiple types of voltage-dependent Ca2+-activated K+ channels of large conductance in rat brain synaptosomal membranes. Biophys. J. 53 , 919–934 (1988).
Kang, J., Huguenard, J. R. & Prince, D. A. Two types of BK channels in immature rat neocortical pyramidal neurons. J. Neurophysiol. 76, 4194–4197 (1996).
Reinhart, P. H., Chung, S. & Levitan, I. B. A family of calcium-dependent potassium channels from rat brain. Neuron 2, 1031– 1041 (1989).
Wei, A, Jegla, T. & Salkoff, L. Eight potassium channel familes revealed by the C. elegans genome project. Neuropharmacology 35 , 805–829 (1996).
Heginbotham, L., Lu, Z., Abramson, T. & MacKinnon, R. Mutations in the K+ channel signature sequence. Biophys.J. 66, 1061–1067 (1994) .
Schreiber, M. et al. Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes. J. Biol. Chem. 273, 3509–3516 (1998).
Papazian, D.M. & Bezanilla, F. How does an ion channel sense voltage? News Physiol. Sci. 12, 203- 210 (1997).
Wallner, M., Meera, P. & Toro, L. Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca2+-sensitive K+ channels: An additional transmembrane region at the N terminus. Proc. Natl Acad. Sci. USA 93, 14922–14927 (1996).
Meera, P., Wallner, M., Song, M. & Toro, L. Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc. Natl Acad. Sci. USA 94, 14066– 14071 (1997).
Ponting, C. P., Phillips, C., Davies, K. E. & Blake, D. J. PDZ domains: targeting signalling molecules to sub-membranous sites. Bioessays 19, 469–479 (1997).
Hanner,M. et al. The beta subunit of the high-conductance calcium-activated potassium channel contributes to the high-affinity receptor for charybdotoxin. Proc. Natl Acad. Sci. USA 94, 2853– 2858 (1997).
Mienville, J. M. & Barker, J. L. Immature properties of large-conductance calcium-activated potassium channels in rat neuroepithelium. Pflugers Arch. 431, 763– 770 (1996).
Hirsch, J. R. & Schlatter, E. Ca2+-dependent K+ channels in the cortical collecting duct of rat. Wien. Klin. Wochenschr. 109, 485–488 (1997).
Kanyicska, B., Freeman, M. E. & Dryer, S. E. Endothelin activates large-conductance K+ channels in rat lactotrophs: reversal by long-term exposure to dopamine agonist. Endocrinology 138, 3141– 3153 (1997).
Knaus, H.-G. et al. Distribution of high-conductance Ca2+-activated K+ channels in rat brain: targeting to axons and nerve terminals. J. Neurosci. 16, 955–963 (1996).
Chang, C. P., Dworetzky, S. I., Wang, J. & Goldstein, M. E. rential expression of the alpha and beta subunits of the large-conductance calcium-activated potassium channel: implication for channel diversity. Mol. Brain Res. 45, 33–40 (1997).
Altschul, S. F., Gish, W., Miller, W., Myers, E.W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol 215, 403–410 (1990).
Joiner, W. J., Wang, L.-Y., Tang, M. & Kaczmarek, L.K. hSK4, a member of a novel subfamily of calcium-activated potassium channels. Proc. Natl Acad. Sci. USA 94, 11013– 11018 (1997).
Acknowledgements
We thank J. Boulter for his gift of the rat brain cDNA library. We also thank J. Trojnacki and J. McCaughern-Carucci for technical assistance. These studies were supported by an NIH grant to L.K.K.
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Joiner, W., Tang, M., Wang, LY. et al. Formation of intermediate-conductance calcium-activated potassium channels by interaction of Slack and Slo subunits. Nat Neurosci 1, 462–469 (1998). https://doi.org/10.1038/2176
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DOI: https://doi.org/10.1038/2176